Drug-Loaded Lipid-Coated Hybrid Organic-Inorganic “Stealth” Nanoparticles for Cancer Therapy

Abstract

Hybrid porous nanoscale metal organic frameworks (nanoMOFs) made of iron trimesate are attracting increasing interest as drug carriers, due to their high drug loading capacity, biodegradability, and biocompatibility. NanoMOF surface modification to prevent clearance by the innate immune system remains still challenging in reason of their high porosity and biodegradable character. Herein, FDA-approved lipids and poly(ethylene glycol) (PEG)-lipid conjugates were used to engineer the surface of nanoMOFs by a rapid and convenient solvent-exchange deposition method. The resulting lipid-coated nanoMOFs were extensively characterized. For the first time, we show that nanoMOF surface modification with lipids affords a better control over drug release and their degradation in biological media. Moreover, when loaded with the anticancer drug Gem-MP (Gemcitabine-monophosphate), iron trimesate nanoMOFs acted as "Trojan horses" carrying the drug inside cancer cells to eradicate them. Most interestingly, the PEG-coated nanoMOFs escaped the capture by macrophages. In a nutshell, versatile PEG-based lipid shells control cell interactions and open perspectives for drug targeting.

Degradation Mechanism of Metal–Organic Framework Drug Nanocarriers Studied by Solid-State Nuclear Magnetic Resonance and X-ray Absorption Near-Edge Structure Spectroscopy

“…In addition, the MIL-100 MOFs consist of coordinative unsaturated metal sites (CUS) with strong Lewis acid properties produced upon thermal activation and departure of labile ligands 9,10 . The high drug payload of nanoMIL-100(Fe) has been demonstrated for various drugs 12,1312,13 , namely anticancer 2,14,15 , antibiotic 16,17 , antiretroviral 18 , and a combination of anti-inflammatory and antibiotics 19 . For example, the anticancer drug busulfan was loaded in nanoMIL-100(Fe) with a payload of 25 wt%, five and sixty times higher than its payload in polymer nanoparticles and in liposomes, respectively 2,20,21 .…”

Solid‐state NMR spectroscopy as a powerful tool to investigate the location of fluorinated lipids in highly porous hybrid organic–inorganic nanoparticles

“…11 In recent studies, it was shown that bulkier lipids such as DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) and PEG-DSPE (1, 2-Distearoyl-sn-glycero-3-phospho-ethanolamine-Poly(ethylene glycol)) remained anchored at the nanoMOF surface without penetrating inside the pores. 14 The porosity of the nanoMOFs was not altered by surface modifications with these FDA-approved lipids (1519 ± 50 m 2 .g -1 , 1486 ± 70 m 2 .g -1 , and 1547 ± 80 m 2 .g -1 for uncoated nanoMOFs, lipid coated nanoMOFs with and without DSPE-PEG 2000, respectively, see Figure S2). Similarly, in this study, nanoMOFs coated with FP which has bulky structure as these previously studied lipids exhibited similar BET surface area (1500 ± 70 m 2 .g -1 ), as compared to the DOPC or DSPE-PEG coated nanoMOFs.…”

“…[8,9] More recently, Food and Drug Administration (FDA)approved lipids and PEG-lipid conjugates were used to coat the surface of nanoMOFs by a rapid and convenient solvent-exchange deposition method. [10] It was shown that nanoMOF surface modification with lipids affords a better control over drug release and particle degradation. Moreover, nanoMOFs acted as "Trojan horses" carrying anticancer drugs inside cancer cells to eradicate them.…”

Research Progress Based on Regulation of Tumor Microenvironment Redox and Drug-Loaded Metal-Organic Frameworks

“…CBD induces mitochondrial dysfunction and ROS production, triggering an apoptotic cascade in glioma cells by regulating the expression of NF-κB. Li et al [56] found that the surface modification of nano-MOFs with lipids can preferably control the degradation of drugs in biological media. When loaded with anticancer medicines such as Gem-MP (gemcitabine-monophosphate), melamine iron nano-MOFs act as "Trojan horses," which carry drugs into tumor cells to destroy them.…”